SEX DIFFERENCES IN MICE EXPOSED TO THE CHRONIC UNPREDICTABLE MILD STRESS MODEL

Major depression is a mood disorder that can cause profound emotional, cognitive, and social impairment. Given its high prevalence, complex etiology, and difficulty establishing effective pharmacotherapy, it is considered a global health problem. Women are 50% more likely to develop the disorder than men and biological factors seem to contribute to this sex difference. Together with anxiety disorders, major depression is the most prevalent psychiatric disorder, and exposure to stressful situations contributes to its development. Based on this close association between chronic stress and the aforementioned conditions, the model of chronic unpredictable mild stress (CUMS) was developed. Although divergences in the neuroendocrine pathways of stress response have been described, sex distinctions in stress response and sensitivity are poorly understood, and CUMS represents a strategic model for a better understanding. Thus, this work aimed to compare the sensitivity to the behavioral effects of stress in male and female mice when subjected to the CUMS model. Adult Swiss mice from both sexes were exposed to a range of environmental stressors for six or eight weeks and, after, were subjected to sucrose preference, spontaneous alternations, social approach, open field, and forced swimming tests (CEUA-UFRJ 100/19). Changes induced by CUMS were detected only in females, which showed a reduction in body weight, higher anxiety in the open field, and a trend-level increase in immobility time during forced swimming, demonstrating that males and females have different stress response mechanisms. Additionally, our results showed sex differences in parameters related to hedonic responses, anxiety, and behavioral despair. In summary, our findings confirm a greater susceptibility to stress in females compared to male Swiss mice. Funding: CAPES, CNPQ and FAPERJ.